The Johns Hopkins University School of Medicine

Office of Research Administration733 North BroadwayBRB, Suite 117

Baltimore, MD 21205

United States

Pre-clinical Testing of Novel Glutamine Metabolic Inhibitors in MYC-driven Medulloblastoma

Background

Medulloblastoma is the most common pediatric brain tumor. While up to 80% of patients are cured, there is a subgroup of patients for whom the current aggressive therapies do not work. These patients have tumors which make large amounts of a protein called MYC. This is a very strong driver of cancer cell growth, but MYC is very hard to target directly.

Targeting LIN28B in DIPG

Brain Tumors, Glioma

Background

Incorporating Cancer Vaccines with Chemotherapy for the Treatment of Osteosarcoma

Osteosarcoma

Background

The most exciting advances in cancer treatment over the last few years have been with immune-based therapies. We have witnessed great successes for adult patients in treating skin, kidney, and lung cancer with antibodies that allow the immune system to be activated against a patient's cancer. Relapsed leukemia is being treated using genetically engineered immune cells that attack the leukemia cells.

RUNX1 Control of the CEBPA enhancer as a Target of Myeloid Transformation

Acute Myeloid Leukemia (AML)

Background

Targeting Notch in Embryonal Tumors

Brain Tumors

Background

Genetic Alterations in Intramedullary Spinal Cord Tumors

Astrocytoma, Ependymoma, Spinal Cord Tumors

Background

Spinal cord tumors are rare neoplasms that occur in children that can result in tremendous disability and eventually mortality. Given their rarity, our understanding of spinal cord tumors is extremely poor. As a result, clinicians are often forced to treat tumors arising in the spinal cord based on data generated from similar tumors arising in the brain. However, there are burgeoning data that suggests that while pediatric brain and spinal cord tumors look identical under a microscope, they are biologically and clinically very different.

Developing a Novel Tumor Model to Screen for New Therapies for Spinal Ependymoma

Ependymoma, Spinal Cord Tumors, Spinal Cord Tumor - Ependymoma

Background

The Cebpa Downstream Enhancer as a Key Target of Transformation to Acute Myeloid Leukemia

Leukemia, Acute Myeloid Leukemia (AML)

Background

Acute myeloid leukemia (AML) accounts for 20% of pediatric leukemias, and despite considerable improvements in treatment, has an approximately 50% mortality rate. Mutations in AML can be classified into two categories: type I that stimulate proliferation, and type II that inhibit normal differentiation. C/EBPa, a protein critical for normal maturation of myeloid cells, is decreased in the majority of AML cases. Previously, the Friedman laboratory identified a DNA region encoding a C/EBPa enhancer, which functions to increase its production.

Targeting Abnormal Metabolism in Neuroblastoma

Brain Tumors, Neuroblastoma

Background

We have demonstrated that inhibitors of glutamine metabolism such as DON, acivicin, and Compound 968 effectively kill medulloblastoma cells and prevent the growth of MYC-driven medulloblastoma orthotopic xenografts. NMYC amplified neuroblastoma also shows increased glutamine metabolism. We do not know if inhibitors of glutamine metabolism will effectively kill neuroblastoma cells.

HMGA1-Targeted Nanoparticles as Novel Therapy for Pediatric Leukemias

Leukemia

Background

The high mobility group A1 (HMGA1) protein plays an important in role during embryonic development, but in cancer the HMGA1 gene becomes re-expressed, stimulating stem cell pathways which enables tumors to rapidly proliferate and evade many conventional treatments. HMGA1 is present in high levels in virtually all aggressive cancers studied to date, including pediatric ALL and AML. Together, ALL and AML are two of the leading causes of death for children with cancer.

Alex's Lemonade Stand Foundation for Childhood Cancer